The object of the proposed research is to increase our understanding of the relationship between structure and biological activity in the actinomycin series. This group of antitumor antibiotics vary structurally only in the peptide moieties, the structure and conformation of which are crucial in determining activity. The work of many investigators on the mode of action of actinomycins and the X-ray crystallographic study of the deoxyguanosine-actinomycin D complex have created a situation in which an opportunity exists to rationalize structure-activity relationships in this field on a molecular basis. The proposed investigations include production of novel actinomycins by directed biosynthesis, structural studies on some new actinomycins, and comparisons of the conformation of several actinomycins by nuclear magnetic resonance and model-building. Conclusions drawn from the latter study will be utilized to formulate a rational approach to structure-activity relationships in this series.